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Variantes genéticas rs1800629 en TNF y rs2228145 en IL6R: asociación con eventos supuestamente atribuibles a la vacunación e inmunización (ESAVI) y anticuerpos neutralizantes contra SARS-CoV-2 en la población del occidente de México vacunada con AZD1222
Genetic variants rs1800629 in TNF and rs2228145 in IL6R: Association with adverse event following immunization (AEFI) and SARS-CoV-2 neutralizing antibodies in western Mexico population that received AZD1222 vaccine
Axel Jair Villa-Panduroa, Narda M. Corona-Reynagaa, Dennis A. Meza-Peñaa, Mayra Alejandra Enciso Ramíreza, Astrid Selene Espinoza Garcíab, Jorge Galindo-Garcíac, Berenice Sanchez-Caballerob, Elia Herminia Valdés-Miramontesb, José Francisco Muñoz-Valled, Zyanya Reyes-Castilloa,b,
Autor para correspondencia
zyanya.reyes@cusur.udg.mx

Autor para correspondencia.
a Laboratorio de Biomedicina y Biotecnología para la Salud, Centro Universitario del Sur, Universidad de Guadalajara, Jalisco, México
b Instituto de Investigaciones en Comportamiento Alimentario y Nutrición, Centro Universitario del Sur, Universidad de Guadalajara, Jalisco, México
c Departamento de Producción Animal, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Jalisco, México
d Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México
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        "titulo" => "Genetic variants rs1800629 in <span class="elsevierStyleItalic">TNF</span> and rs2228145 in <span class="elsevierStyleItalic">IL6R&#58;</span> Association with adverse event following immunization &#40;AEFI&#41; and SARS-CoV-2 neutralizing antibodies in western Mexico population that received AZD1222 vaccine"
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          "es" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">a&#41; Porcentajes de neutralizaci&#243;n contra la prote&#237;na espiga del SARS-CoV-2 con respecto al sexo&#59; prueba U de Mann-Whitney&#46; b&#41; Porcentajes de neutralizaci&#243;n contra la prote&#237;na S del SARS-CoV-2 con respecto a los genotipos de la variante rs1800629&#59; prueba U de Mann-Whitney&#46; c&#41; Porcentajes de neutralizaci&#243;n contra la prote&#237;na S del SARS-CoV-2 con respecto a los genotipos de la variante rs2228145&#59; prueba Kruskal-Wallis&#46; Las l&#237;neas horizontales representan mediana y rango intercuartil &#40;P25&#37;-P75&#37;&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Introducci&#243;n</span><p id="p0005" class="elsevierStylePara elsevierViewall">La pandemia por el virus del s&#237;ndrome respiratorio agudo severo por coronavirus 2 &#40;SARS-CoV-2&#41; causante de la COVID-19 y su r&#225;pida dispersi&#243;n a nivel mundial&#44; favoreci&#243; el desarrollo y la aplicaci&#243;n de vacunas en un breve lapso de tiempo para controlar la propagaci&#243;n del virus y reducir la severidad y letalidad de la COVID-19<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>&#46; M&#233;xico report&#243; una de las tasas de letalidad m&#225;s alta a nivel mundial &#40;11-13&#37;&#41; y aunque son m&#250;ltiples los factores asociados a una mayor mortalidad<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a>&#44; se ha reconocido que la gen&#233;tica del hospedero puede jugar un papel importante en la susceptibilidad a la infecci&#243;n y en la severidad de la misma e incidir en la respuesta inmune inducida por vacunas&#44; as&#237; como en los efectos posteriores a su aplicaci&#243;n<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="p0010" class="elsevierStylePara elsevierViewall">En la regi&#243;n occidente de M&#233;xico&#44; la vacuna AZD1222 &#40;AstraZeneca&#44; Universidad de Oxford&#41; ha sido una de las m&#225;s aplicadas&#59; esta se basa en un vector v&#237;rico recombinante no replicativo de tipo adenovirus&#44; que contiene informaci&#243;n codificada para producir la prote&#237;na espiga &#40;S&#41; del SARS-CoV-2&#44; estimulando la respuesta inmune humoral y celular<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a>&#46; La prote&#237;na S es un sitio antig&#233;nico importante al cual se unen los anticuerpos neutralizantes producidos por el hospedero para bloquear la entrada del virus<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a>&#44; por lo que es clave en el dise&#241;o de las vacunas como AZD1222&#46; Los eventos supuestamente atribuibles a la vacunaci&#243;n o inmunizaci&#243;n &#40;ESAVI&#41; denotan un evento cl&#237;nico desfavorable y no intencionado posterior a la vacunaci&#243;n&#44; sin ser necesaria la relaci&#243;n causal con el proceso de inmunizaci&#243;n o la propia vacuna<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a>&#46; Los ESAVI m&#225;s frecuentemente relacionados con la vacuna de AZD1222 son dolor en la zona de aplicaci&#243;n&#44; cefalea&#44; mialgia&#44; fatiga&#44; artralgia y fiebre<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">Por otro lado&#44; el factor de necrosis tumoral alfa &#40;TNF-&#945;&#41; es una citoquina proinflamatoria y un regulador clave del sistema inmune innato y adaptativo&#59; participa en el reclutamiento de linfocitos a las zonas de infecci&#243;n&#44; activa las c&#233;lulas presentadoras de ant&#237;geno y puede activar al linfocito B por la v&#237;a independiente de linfocitos T&#44; permitiendo su proliferaci&#243;n y diferenciaci&#243;n a c&#233;lulas plasm&#225;ticas productoras de anticuerpos<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a>&#46; El gen que la codifica es el <span class="elsevierStyleItalic">TNF</span> y es altamente polim&#243;rfico&#46; La variante rs1800629 est&#225; situada en la regi&#243;n promotora del gen <span class="elsevierStyleItalic">TNF</span> y se ha sugerido que tiene un efecto en su expresi&#243;n g&#233;nica&#44; al existir mayor expresi&#243;n de TNF-&#945; en los individuos con genotipos GA y AA&#44; respecto a los portadores del genotipo GG<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a>&#46; Por su parte&#44; la citoquina IL-6 es un inductor importante de la respuesta de fase aguda que regula genes implicados en la diferenciaci&#243;n&#44; supervivencia&#44; apoptosis y proliferaci&#243;n celular&#59; para su se&#241;alizaci&#243;n&#44; requiere de la interacci&#243;n con el receptor de IL-6 &#40;IL-6R&#41; el cual se puede presentar de 2 formas&#58; transmembranal y soluble<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a>&#46; El gen que se encarga de codificar este receptor es <span class="elsevierStyleItalic">IL6R</span> y es altamente polim&#243;rfico<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a>&#46; La variante gen&#233;tica rs2228145 se encuentra en el ex&#243;n 9 de <span class="elsevierStyleItalic">IL6R</span> y conduce a una sustituci&#243;n de amino&#225;cido a nivel de prote&#237;na &#40;&#225;cido asp&#225;rtico &#91;Asp&#93; por alanina &#91;Ala&#93;&#41; en la posici&#243;n 358 dentro del dominio extracelular de IL-6R<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a>&#46; Se ha sugerido que este polimorfismo induce mayor desprendimiento de IL-6R de la superficie celular provocando alteraci&#243;n en la v&#237;a IL-6 cl&#225;sica<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> y el alelo C &#40;358 Ala&#41; se ha asociado con concentraciones aumentadas de sIL-6R circulante<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a>&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">La respuesta inmune generada posvacunaci&#243;n podr&#237;a verse afectada por la presencia de variantes en genes del sistema inmune&#44; como ha sido reportado previamente para la vacuna contra el sarampi&#243;n&#44; la rub&#233;ola&#44; la hepatitis B&#44; entre otras<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a>&#46; En este sentido&#44; la presencia del genotipo polim&#243;rfico AA de rs1800629 en <span class="elsevierStyleItalic">TNF</span>&#44; fue previamente asociada con una producci&#243;n baja de anticuerpos para la vacuna contra la hepatitis B<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a>&#46; En otro estudio se encontr&#243; una tasa baja de seroconversi&#243;n en los portadores de esta variante al recibir la vacuna contra la encefalitis japonesa&#44; sin llegar a ser significativa<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>&#46; Por su parte&#44; el alelo C del polimorfismo rs2228145 en <span class="elsevierStyleItalic">IL6R</span> se ha asociado con enfermedades como la esclerosis lateral amiotr&#243;fica<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a>&#44; as&#237; como el desarrollo de Alzheimer de inicio temprano<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> y el desarrollo de diabetes tipo 1 en la edad adulta<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">Actualmente no existen estudios que asocien a las variantes rs1800629 y rs228145 en <span class="elsevierStyleItalic">TNF</span> e <span class="elsevierStyleItalic">IL6R</span>&#44; con la producci&#243;n de anticuerpos neutralizantes contra SARS-CoV-2 tras recibir el esquema de vacunaci&#243;n AZD1222&#59; adem&#225;s&#44; la respuesta de los individuos inmunizados es heterog&#233;nea y no se cuenta con datos suficientes para conocer la producci&#243;n de anticuerpos tras recibir dicho esquema&#44; por lo cual&#44; en esta investigaci&#243;n se plante&#243; estudiar a la poblaci&#243;n adulta del occidente de M&#233;xico vacunada con el esquema AZD1222&#44; con el objetivo de evaluar si ambas variantes en genes de respuesta inmune son un factor gen&#233;tico asociado a la producci&#243;n de anticuerpos neutralizantes generados por la vacuna AZD1222 y a la frecuencia de ESAVI&#46; La investigaci&#243;n sobre los factores inmunogen&#233;ticos asociados a la respuesta posvacunaci&#243;n es relevante&#44; dado que puede explicar la heterogeneidad de esta respuesta en la poblaci&#243;n de estudio&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Material y m&#233;todo</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Dise&#241;o y sede del estudio</span><p id="p0030" class="elsevierStylePara elsevierViewall">El presente estudio fue de tipo transversal-anal&#237;tico&#44; los participantes asistieron al Laboratorio de Biomedicina y Biotecnolog&#237;a para la Salud en el Centro Universitario del Sur de la Universidad de Guadalajara &#40;en el periodo octubre 2021-febrero 2022&#41;&#44; donde se realiz&#243; la obtenci&#243;n de una muestra sangu&#237;nea para la separaci&#243;n de suero y extracci&#243;n de ADN gen&#243;mico &#40;ADNg&#41;&#46; Durante la misma visita&#44; se aplic&#243; una encuesta de datos sociodemogr&#225;ficos&#44; el cuestionario de frecuencia ESAVI y se realiz&#243; la evaluaci&#243;n antropom&#233;trica de los participantes&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Participantes</span><p id="p0035" class="elsevierStylePara elsevierViewall">Los participantes fueron reclutados por invitaci&#243;n&#46; El c&#225;lculo del tama&#241;o de la muestra se realiz&#243; utilizando el programa OpenEpi &#40;v&#46; 3&#41;&#44; utilizando las frecuencias genot&#237;picas reportadas por SNPedia en la poblaci&#243;n con ancestr&#237;a mexicana &#40;con residencia en Los &#193;ngeles&#44; EE&#46; UU&#46;&#41; para la variante rs1800629&#46; Se obtuvo una <span class="elsevierStyleItalic">n</span> &#61; 116 con un poder estad&#237;stico de 80&#37; y nivel de confianza de 90&#37;&#46; Se incluy&#243; un total de 117 participantes&#44; 38&#37; hombres &#40;<span class="elsevierStyleItalic">n &#61;</span> 45&#41; y 62&#37; mujeres &#40;<span class="elsevierStyleItalic">n &#61;</span> 72&#41;&#44; con un rango de edad entre 18 y 60 a&#241;os&#46; Los criterios de inclusi&#243;n fueron&#58; contar con esquema de vacunaci&#243;n AZD1222 de 2 dosis&#44; contar con al menos 15 d&#237;as de la aplicaci&#243;n de la &#250;ltima dosis y ser mestizo mexicano&#44; con ancestr&#237;a de por lo menos 3 generaciones anteriores del occidente de M&#233;xico&#59; los criterios de exclusi&#243;n fueron&#58; contar con otro&#40;s&#41; esquema&#40;s&#41; de vacunaci&#243;n contra SARS-CoV-2&#44; estar embarazada&#44; estar en tratamiento con inmunosupresores&#44; presentar s&#237;ntomas o infecci&#243;n confirmada de SARS-CoV-2 o de otras enfermedades infecciosas al momento de la toma de la muestra&#46;</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Composici&#243;n corporal y antropometr&#237;a</span><p id="p0040" class="elsevierStylePara elsevierViewall">Se realiz&#243; la evaluaci&#243;n antropom&#233;trica de los participantes&#44; siguiendo los lineamientos establecidos por la Sociedad Internacional para el Avance de la Cineantropometr&#237;a &#40;ISAK&#41;&#46; La medici&#243;n de peso &#40;kg&#41; y grasa corporal &#40;&#37;&#41; se realiz&#243; con un monitor de grasa corporal y b&#225;scula de bioimpedancia &#40;BF-679W&#44; Tanita&#44; Jap&#243;n&#41;&#44; la talla &#40;cm&#41; con estadi&#243;metro port&#225;til &#40;213 l&#44; SECA&#44; EE&#46; UU&#46;&#41;&#44; mientras que la circunferencia de cintura y cadera &#40;cm&#41; se midi&#243; con cinta antropom&#233;trica &#40;Lufkin&#44; EE&#46; UU&#46;&#41;&#46;</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Cuantificaci&#243;n de anticuerpos neutralizantes contra la prote&#237;na S del SARS-CoV-2</span><p id="p0045" class="elsevierStylePara elsevierViewall">La recolecci&#243;n de la muestra sangu&#237;nea de los participantes se realiz&#243; por venopunci&#243;n en tubos para suero&#46; Los sueros se separaron por procedimientos estandarizados y se almacenaron a -60 &#176;C&#46; La cuantificaci&#243;n del porcentaje de anticuerpos neutralizantes contra SARS-CoV-2 se realiz&#243; mediante el ensayo cPass SARS-CoV-2 <span class="elsevierStyleItalic">Neutralization Antibody Detection Kit</span> &#40;GenScript&#44; China&#41; basado en un ensayo de inmunoadsorci&#243;n ligado a enzimas &#40;ELISA&#41; por bloqueo&#46; El protocolo se realiz&#243; de acuerdo con las instrucciones del fabricante&#46; La lectura de absorbancia fue a 450 nm y los porcentajes de neutralizaci&#243;n se calcularon utilizando la f&#243;rmula proporcionada por el fabricante&#58; porcentaje de neutralizaci&#243;n &#61; 1- &#40;Valor densidad &#243;ptica &#91;DO&#93; de la muestra&#47;Valor DO del control negativo&#41; x100&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Extracci&#243;n de ADN gen&#243;mico</span><p id="p0050" class="elsevierStylePara elsevierViewall">Se extrajo una muestra sangu&#237;nea por venopunci&#243;n&#44; a partir de la cual se realiz&#243; la extracci&#243;n de ADNg mediante el kit <span class="elsevierStyleItalic">QIAamp DNA Blood Mini Kit</span> &#40;QIAGEN&#44; Alemania&#41; siguiendo la metodolog&#237;a especificada por el fabricante&#46; La cantidad y calidad del ADNg obtenido fue verificado por medio de la medici&#243;n de la densidad &#243;ptica a 260 y 280 nm en un espectrofot&#243;metro &#40;Multiskan&#44; Thermo Fischer Scientific&#44; EE&#46; UU&#41;&#46;</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Identificaci&#243;n de genotipos de las variantes rs1800629 y rs2228145</span><p id="p0055" class="elsevierStylePara elsevierViewall">La identificaci&#243;n de las variantes rs1800629 y rs2228145 se realiz&#243; por amplificaci&#243;n mediante la reacci&#243;n en cadena de la polimerasa en tiempo real &#40;qPCR&#41;&#44; utilizando sondas Taqman &#40;C&#95;7514879&#95;10 y C&#95;16170664&#95;10&#44; Applied Biosystems&#44; EE&#46; UU&#46;&#41;&#46; Los reactivos fueron preparados seg&#250;n las recomendaciones del fabricante de la siguiente manera&#58; 5 &#956;l de TaqMan Master Mix&#59; 0&#44;5 &#956;l TaqMan SNP Genotyping Assay&#59; &#8764;<span class="elsevierStyleHsp" style=""></span>50 ng de ADNg&#59; &#8764;3&#44;5 &#956;l de agua est&#233;ril&#44; completando un volumen de 10 &#956;l por reacci&#243;n&#46; La qPCR se realiz&#243; en el termociclador QuantStudio5 &#40;Applied Biosystems&#44; EE&#46; UU&#46;&#41;&#44; con las siguientes condiciones&#58; activaci&#243;n de la polimerasa a 95 &#176;C por 10 minutos&#44; desnaturalizaci&#243;n a 95 &#176;C por 15 segundos&#44; alineaci&#243;n y extensi&#243;n a 60 &#176;C por un minuto&#59; todo lo anterior por 40 ciclos&#46; Como control negativo y controles positivos&#44; se utiliz&#243; agua libre de ADNasas y muestras de ADN con genotipos conocidos&#44; respectivamente&#46; La identificaci&#243;n de los genotipos se realiz&#243; mediante el software QuantStudio Design &#38; Analysis Software v1&#46;5&#46;2 &#40;Applied Biosystems&#44; EE&#46; UU&#46;&#41;&#46;</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">An&#225;lisis estad&#237;stico</span><p id="p0060" class="elsevierStylePara elsevierViewall">Los datos fueron analizados y graficados mediante el software GraphPad Prism Ve&#46;8&#46;0&#46;1 &#40;GraphPad Software LLC&#41;&#46; La distribuci&#243;n de datos se verific&#243; con la prueba de normalidad de Kolmogorov-Smirnov y el test D&#8217;Agostino&#46; Se realizaron an&#225;lisis comparativos de los niveles de anticuerpos con base en el sexo o el genotipo&#59; las variables continuas con distribuci&#243;n normal fueron comparadas mediante pruebas param&#233;tricas &#40;T Student o ANOVA&#41; y aquellas con distribuci&#243;n no normal fueron comparadas mediante pruebas no param&#233;tricas &#40;U de Mann-Whitney o Kruskal-Wallis&#41;&#46; Las variables categ&#243;ricas se expresaron como porcentaje y frecuencias&#44; se analizaron mediante prueba de Chi-cuadrada o prueba exacta de Fisher&#44; seg&#250;n corresponda&#46; Se consider&#243; un nivel de significancia de <span class="elsevierStyleItalic">p</span> &#60; 0&#44;05&#46;</p></span></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Resultados</span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Caracter&#237;sticas sociodemogr&#225;ficas&#44; antropom&#233;tricas y antecedentes cl&#237;nicos de los participantes</span><p id="p0065" class="elsevierStylePara elsevierViewall">Las caracter&#237;sticas sociodemogr&#225;ficas&#44; antropom&#233;tricas y antecedentes cl&#237;nicos de los participantes se muestran en la <a class="elsevierStyleCrossRef" href="#t0005">tabla 1</a>&#46; Se evaluaron un total de 117 individuos con una mediana de 36 &#40;22-58&#41; d&#237;as posvacunaci&#243;n&#44; los cuales se separaron considerando el sexo de los participantes&#46; Se encontraron diferencias significativas con respecto a la edad &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0274&#41; y el porcentaje de grasa corporal &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0001&#41;&#44; siendo mayores en el grupo femenino&#46; El peso &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0010&#41;&#44; la talla &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#44;0001&#41; y la circunferencia de cintura &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0043&#41; fueron mayores en el grupo masculino&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0120">Frecuencias genot&#237;picas y al&#233;licas de las variantes rs1800629 en <span class="elsevierStyleItalic">TNF</span> y rs2228145 en <span class="elsevierStyleItalic">IL6R</span></span><p id="p0070" class="elsevierStylePara elsevierViewall">Se identificaron 2 de los 3 genotipos de la variante rs1800629&#58; el homocigoto silvestre GG con 86&#44;3&#37; &#40;<span class="elsevierStyleItalic">n &#61;</span> 101&#41; y el heterocigoto polim&#243;rfico GA con 13&#44;7&#37; &#40;<span class="elsevierStyleItalic">n &#61;</span> 16&#41;&#59; siendo nula la presencia del homocigoto polim&#243;rfico AA&#46; Se determin&#243; que las frecuencias genot&#237;picas de esta variante se encontraban en equilibrio de Hardy-Weinberg &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;728&#41;&#46; En el caso de la variante rs2228145&#44; se identificaron los 3 genotipos&#58; el homocigoto AA con el 20&#37; &#40;<span class="elsevierStyleItalic">n &#61;</span> 25&#41;&#44; el heterocigoto polim&#243;rfico CA con 48&#37; &#40;<span class="elsevierStyleItalic">n &#61;</span> 55&#41; y el homocigoto polim&#243;rfico con el 32&#37; &#40;<span class="elsevierStyleItalic">n &#61;</span> 37&#41;&#46; Se determin&#243; que las frecuencias genot&#237;picas de esta variante se encontraban en equilibrio de Hardy-Weinberg &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;9243&#41;&#44; por lo que se infiere que en la poblaci&#243;n de estudio hubo una selecci&#243;n aleatoria&#44; no existen tasas altas de mutaci&#243;n&#44; no se presenta migraci&#243;n u otros fen&#243;menos que causen su desviaci&#243;n&#46; Las frecuencias genot&#237;picas y al&#233;licas de ambas variantes se muestran detalladamente en la <a class="elsevierStyleCrossRef" href="#t0010">tabla 2</a>&#46; No se encontraron diferencias significativas al comparar la frecuencias genot&#237;picas y al&#233;licas con base en el sexo&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0125">An&#225;lisis de anticuerpos neutralizantes contra SARS-CoV-2 con respecto al sexo</span><p id="p0075" class="elsevierStylePara elsevierViewall">Los porcentajes de anticuerpos neutralizantes generados contra la prote&#237;na S del SARS-CoV-2 en poblaci&#243;n con el esquema AZD1222 con base en el sexo&#44; se muestran en la <a class="elsevierStyleCrossRef" href="#f0005">figura 1</a>A&#46; No se encontraron diferencias significativas en los porcentajes de neutralizaci&#243;n entre los grupos de estudio&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0130">An&#225;lisis de anticuerpos neutralizantes contra SARS-CoV-2 con respecto al genotipo de las variantes rs1800629 y rs2228145</span><p id="p0080" class="elsevierStylePara elsevierViewall">Se analizaron los porcentajes de neutralizaci&#243;n contra la prote&#237;na S del SARS-CoV-2 con base en los genotipos de la variante rs1800629&#44; estos fueron muy similares entre s&#237;&#44; por lo que no se encontraron diferencias significativas entre los genotipos de <span class="elsevierStyleItalic">TNF</span> &#40;<span class="elsevierStyleItalic">p &#61;</span> 0&#44;4323&#41; &#40;<a class="elsevierStyleCrossRef" href="#f0005">fig&#46; 1</a>B&#41;&#46; Considerando que la mayor&#237;a de participantes present&#243; porcentajes muy altos de anticuerpos neutralizantes posvacunaci&#243;n AZD1222 &#40;superiores a 90&#37; de neutralizaci&#243;n&#41;&#44; se realiz&#243; un suban&#225;lisis por genotipos en el gen de <span class="elsevierStyleItalic">TNF</span>&#44; incluyendo &#250;nicamente a los participantes que presentaron porcentajes de anticuerpos menores a 90&#37; de neutralizaci&#243;n&#46; Sin embargo&#44; no se encontr&#243; relaci&#243;n significativa entre los porcentajes de neutralizaci&#243;n menores a 90&#37; con los genotipos de la variante rs1800629 &#40;datos no mostrados&#41;&#46;</p><p id="p0085" class="elsevierStylePara elsevierViewall">Se realiz&#243; el an&#225;lisis de los porcentajes de neutralizaci&#243;n contra la prote&#237;na S del SARS-CoV-2 con base en los genotipos de la variante rs2228145&#59; se obtuvo una mediana similar para los 3 genotipos&#44; por lo que no se encontraron diferencias significativas con base en los genotipos de <span class="elsevierStyleItalic">IL6R</span> &#40;<a class="elsevierStyleCrossRef" href="#f0005">fig&#46; 1</a>C&#41;&#46;</p></span><span id="s0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0135">Frecuencia de eventos supuestamente atribuibles a la vacunaci&#243;n e inmunizaci&#243;n&#58; asociaci&#243;n con el sexo y los genotipos de las variantes rs1800629 y rs2228145</span><p id="p0090" class="elsevierStylePara elsevierViewall">Los principales ESAVI reportados por los participantes se muestran en la <a class="elsevierStyleCrossRef" href="#t0015">tabla 3</a>&#46; Se encontr&#243; asociaci&#243;n entre el sexo con respecto a la adinamia &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0243&#41;&#44; escalofr&#237;os &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0085&#41;&#44; artralgia &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0227&#41; y dolor en el &#225;rea de aplicaci&#243;n &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0096&#41;&#59; presentando mayor frecuencia en el grupo femenino&#46; No se encontr&#243; asociaci&#243;n entre el sexo de los participantes con respecto al resto de ESAVI&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia><p id="p0095" class="elsevierStylePara elsevierViewall">Los principales ESAVI con base en los genotipos de la variante rs1800629 del gen <span class="elsevierStyleItalic">TNF</span> y la variante rs2228145 del gen <span class="elsevierStyleItalic">IL6R</span> reportados por los participantes se muestran en la <a class="elsevierStyleCrossRef" href="#t0020">tabla 4</a>&#46; Se encontr&#243; asociaci&#243;n entre los genotipos de la variante rs1800629 con los ESAVI fiebre &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0131&#41; y artralgia &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#44;0058&#41;&#44; siendo ambos m&#225;s frecuentes en los participantes del grupo con el genotipo GA respecto al genotipo GG&#46; No se encontr&#243; asociaci&#243;n de la variante rs1800629 de <span class="elsevierStyleItalic">TNF</span> con el resto de ESAVI&#46; Con respecto a los genotipos de la variante rs2228145 en <span class="elsevierStyleItalic">IL6R&#44;</span> no se encontr&#243; asociaci&#243;n con los ESAVI reportados por los participantes&#46;</p><elsevierMultimedia ident="t0020"></elsevierMultimedia></span></span><span id="s0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0140">Discusi&#243;n</span><p id="p0100" class="elsevierStylePara elsevierViewall">En este estudio se evalu&#243; por primera vez la asociaci&#243;n de las variantes rs1800629 en <span class="elsevierStyleItalic">TNF</span> y rs2228145 en <span class="elsevierStyleItalic">IL6R</span> con la producci&#243;n de anticuerpos neutralizantes contra SARS-CoV-2 y la frecuencia de ESAVI en la poblaci&#243;n adulta del occidente de M&#233;xico con esquema de vacunaci&#243;n AZD1222&#46;</p><p id="p0105" class="elsevierStylePara elsevierViewall">Respecto a las frecuencias genot&#237;picas y al&#233;licas de las variantes rs1800629 en el gen de <span class="elsevierStyleItalic">TNF</span> y rs2228145 en <span class="elsevierStyleItalic">IL6R&#44;</span> la distribuci&#243;n coincide con lo previamente reportado en la poblaci&#243;n mexicana<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a>&#46; Con respecto a los porcentajes de anticuerpos neutralizantes&#44; Chau et al&#46; &#40;2022&#41; determinaron que los niveles de anticuerpos neutralizantes contra SARS-CoV-2 se mantuvieron similares entre los hombres y las mujeres<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a>&#46; Adem&#225;s&#44; se ha reportado que no existe una diferencia entre los niveles de anticuerpos neutralizantes en individuos vacunados respecto a aquellos que los generaron postinfecci&#243;n y que dicha respuesta tampoco se asocia con el sexo de los participantes<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a>&#46; Por lo anterior&#44; nuestros resultados coinciden con investigaciones previas&#44; pero es importante destacar que el promedio de d&#237;as &#40;36&#41; posvacunaci&#243;n de nuestros participantes fue relativamente corto y eso puede explicar los altos porcentajes de anticuerpos neutralizantes detectados contra la prote&#237;na S del SARS-CoV-2 &#40;&#62;<span class="elsevierStyleHsp" style=""></span>90&#37;&#41;&#46; Se reconoce que la producci&#243;n de anticuerpos neutralizantes contra SARS-CoV-2&#44; ya sea por infecci&#243;n natural o tras la vacunaci&#243;n con AZD1221&#44; tiende a disminuir con el tiempo&#46;</p><p id="p0110" class="elsevierStylePara elsevierViewall">No encontramos una asociaci&#243;n entre la producci&#243;n de anticuerpos neutralizantes posvacunaci&#243;n AZD1222 con las 2 variantes gen&#233;ticas evaluadas&#46; Respecto a la variante rs1800629 en <span class="elsevierStyleItalic">TNF</span> no existe literatura que haya evaluado esta relaci&#243;n&#59; sin embargo&#44; Yao et al&#46; &#40;2020&#41; no encontraron una asociaci&#243;n entre la variante rs1800629 y la producci&#243;n de anticuerpos tras la inmunizaci&#243;n con la vacuna contra la encefalitis japonesa<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a>&#46; Otro estudio report&#243; una asociaci&#243;n entre el promedio de anticuerpos y la presencia de la variante rs1800629 tras recibir la vacuna contra la hepatitis B<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a>&#46; Caso contrario&#44; otros autores no han reportado una asociaci&#243;n entre la variante rs1800629 y los bajos niveles de anticuerpos en los individuos inmunizados con la vacuna contra la hepatitis B<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a>&#46; Respecto a la variante rs2228145 en <span class="elsevierStyleItalic">IL6R</span>&#44; no existen publicaciones que eval&#250;en su asociaci&#243;n con la producci&#243;n de anticuerpos neutralizantes tras la inmunizaci&#243;n con AZD1222&#44; sin embargo&#44; una investigaci&#243;n en poblaci&#243;n iran&#237;&#44; evalu&#243; la asociaci&#243;n entre la variante rs2228145 con la susceptibilidad de desarrollar COVID-19&#44; mostrando que los participantes que portan el alelo A en <span class="elsevierStyleItalic">IL6R</span> son m&#225;s susceptibles a desarrollar COVID-19<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a>&#46;</p><p id="p0115" class="elsevierStylePara elsevierViewall">En nuestro estudio&#44; el grupo vacunado con AZD1222 de sexo femenino present&#243; una mayor frecuencia de todos los ESAVI&#44; con excepci&#243;n de la limitaci&#243;n de movimiento&#46; La evidencia sugiere que las diferencias inmunol&#243;gicas&#44; hormonales&#44; gen&#233;ticas e incluso de microbiota intestinal con base en el sexo pueden modular la actividad del sistema inmunitario&#44; pudiendo influir en el resultado de la respuesta ante la vacunaci&#243;n<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a>&#46; Adem&#225;s&#44; se demostr&#243; que&#44; tras la inmunizaci&#243;n contra los virus de la influenza&#44; parotiditis&#44; hepatitis A y B&#44; viruela y dengue&#44; las mujeres desarrollan reacciones adversas m&#225;s frecuentes y graves&#44; como fiebre&#44; dolor e inflamaci&#243;n a las vacunas<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a>&#46; Tran et al&#46; &#40;2021&#41;&#44; determinaron que los ESAVI m&#225;s frecuentes en los individuos inmunizados con AZD1222 fueron fiebre&#44; mialgia&#44; fatiga&#44; dolor en la zona de aplicaci&#243;n y escalofr&#237;os&#46; De forma similar a nuestro estudio&#44; encontraron que el grupo femenino present&#243; ESAVI con mayor frecuencia en comparaci&#243;n con el grupo masculino<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a>&#46; Otro estudio&#44; no report&#243; asociaci&#243;n entre la frecuencia de ESAVI con el sexo tras la aplicaci&#243;n de la primera dosis de AZD1222<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a>&#59; sin embargo&#44; cabe destacar que los participantes de nuestra investigaci&#243;n contaban con 2 dosis de AZD1222&#46;</p><p id="p0120" class="elsevierStylePara elsevierViewall">Al analizar la relaci&#243;n entre las variantes gen&#233;ticas en <span class="elsevierStyleItalic">TNF</span> e <span class="elsevierStyleItalic">IL6R</span> con la frecuencia de ESAVI tras recibir la vacuna AZD1222&#44; se encontr&#243; que el genotipo GA de la variante rs1800629 en <span class="elsevierStyleItalic">TNF</span> se asoci&#243; con mayor frecuencia de fiebre y artralgia posvacunaci&#243;n y se observ&#243; una tendencia a presentar mialgia con mayor frecuencia en los participantes portadores de este genotipo&#46; No existen reportes previos sobre esta asociaci&#243;n&#44; sin embargo&#44; al considerar que TNF-&#945; es una citoquina proinflamatoria&#44; la asociaci&#243;n con estos s&#237;ntomas podr&#237;a deberse a los efectos fisiol&#243;gicos inducidos por esta y posiblemente&#44; una mayor expresi&#243;n y producci&#243;n de TNF-&#945; en los portadores del genotipo GA&#46; Se reconoce que esta citoquina tiene efectos fisiol&#243;gicos vinculados al dolor y al aumento de temperatura<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a>&#46; Algunas citoquinas cuentan con la capacidad de inducir la s&#237;ntesis de prostaglandina en los tejidos perif&#233;ricos&#44; lo que podr&#237;a explicar por qu&#233; esta sintomatolog&#237;a suele acompa&#241;arse del desarrollo de mialgia y artralgia<a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a>&#46; Con respecto al efecto de esta variante gen&#233;tica en la expresi&#243;n de la citoquina&#44; se ha reportado que la variante rs1800629 puede aumentar los niveles de expresi&#243;n del gen <span class="elsevierStyleItalic">TNF</span><a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a>&#59; sin embargo&#44; la evidencia disponible es controversial<a class="elsevierStyleCrossRef" href="#bb0160"><span class="elsevierStyleSup">32</span></a>&#44; por lo que es importante confirmar experimentalmente el efecto biol&#243;gico o funcional de esta variante&#46;</p><p id="p0125" class="elsevierStylePara elsevierViewall">Dentro de las limitaciones de esta investigaci&#243;n se encuentra el tama&#241;o de la muestra&#44; por lo cual recomendamos replicar el estudio en otras poblaciones y con un tama&#241;o de muestra mayor&#59; considerar otras caracter&#237;sticas sociodemogr&#225;ficas o antropom&#233;tricas de la poblaci&#243;n y su relaci&#243;n con los porcentajes de neutralizaci&#243;n&#59; as&#237; como tomar en cuenta los d&#237;as posvacunaci&#243;n y cuantificar los niveles s&#233;ricos de TNF-&#945; e IL-6R soluble para determinar si estos presentan alg&#250;n cambio posterior a la inmunizaci&#243;n y si se asocian con la presencia de ESAVI&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; nuestro estudio confirma un alto porcentaje de anticuerpos neutralizantes generados contra la prote&#237;na S del SARS-CoV-2 en los individuos que recibieron la vacuna AZD1222 con un promedio de 36 &#40;22-58&#41; d&#237;as posvacunaci&#243;n&#46; Los ESAVI adinamia&#44; escalofr&#237;os&#44; artralgia y dolor en el &#225;rea de aplicaci&#243;n tuvieron una incidencia mayor en el grupo femenino&#44; pero solamente fiebre y artralgia mostraron una asociaci&#243;n con la variante rs1800629 en <span class="elsevierStyleItalic">TNF</span> en esta poblaci&#243;n mexicana&#46;</p></span><span id="s0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0145">Responsabilidades &#233;ticas</span><p id="p0135" class="elsevierStylePara elsevierViewall">La presente investigaci&#243;n fue aprobada por el Comit&#233; de &#201;tica del Centro Universitario del Sur de la Universidad de Guadalajara&#44; con c&#243;digo de registro&#58; CEI&#47;046&#47;2021 y el Comit&#233; T&#233;cnico de Investigaci&#243;n&#44; con c&#243;digo de registro&#58; SAC&#47;CIP&#47;019&#47;2021&#46; Adem&#225;s&#44; se siguieron los principios establecidos en la declaraci&#243;n de Helsinki&#46;</p></span><span id="s0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0150">Consentimiento informado</span><p id="p0140" class="elsevierStylePara elsevierViewall">Los individuos en el presente estudio participaron de forma voluntaria y firmaron la carta de consentimiento informado&#46;</p></span><span id="s0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0155">Financiaci&#243;n</span><p id="p0145" class="elsevierStylePara elsevierViewall">Este proyecto fue financiado por el Centro Universitario del Sur de la Universidad de Guadalajara&#44; bajo la Convocatoria de Fortalecimiento de Cuerpos Acad&#233;micos&#44; registro&#58; SAC&#47;CIP&#47;019&#47;2021 otorgado a Zyanya Reyes-Castillo&#46;</p></span><span id="s0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0160">Conflicto de intereses</span><p id="p0150" class="elsevierStylePara elsevierViewall">Ninguno&#46;</p></span></span>"
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        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Introducci&#243;n</span><p id="sp0070" class="elsevierStyleSimplePara elsevierViewall">en esta investigaci&#243;n se evalu&#243; la asociaci&#243;n de las variantes gen&#233;ticas rs1800629 en <span class="elsevierStyleItalic">TNF</span> y rs2228145 en <span class="elsevierStyleItalic">IL6R</span> con la producci&#243;n de anticuerpos neutralizantes contra SARS-CoV-2 y la frecuencia de eventos supuestamente atribuibles a la vacunaci&#243;n o inmunizaci&#243;n &#40;ESAVI&#41; en la poblaci&#243;n adulta del occidente de M&#233;xico con esquema de vacunaci&#243;n AZD1222&#46;</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">M&#233;todos</span><p id="sp0075" class="elsevierStyleSimplePara elsevierViewall">se evaluaron 117 adultos &#40;33 a&#241;os &#91;23-40&#93;&#44; 65&#37; mujeres&#41;&#46; Se registr&#243; la frecuencia autoreportada de ESAVI y se cuantific&#243; el porcentaje de anticuerpos neutralizantes posvacunaci&#243;n&#46; La identificaci&#243;n de las variantes gen&#233;ticas rs1800629 y rs2228145 se realiz&#243; mediante qPCR&#46;</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Resultados</span><p id="sp0080" class="elsevierStyleSimplePara elsevierViewall">la frecuencia de los genotipos de la variante rs1800629 en <span class="elsevierStyleItalic">TNF</span> fue&#58; GG &#40;86&#37;&#41; y GA &#40;14&#37;&#41; y de la variante rs2228145 en <span class="elsevierStyleItalic">IL6R</span>&#58; AA &#40;20&#37;&#41;&#44; CA &#40;48&#37;&#41; y CC &#40;32&#37;&#41;&#46; El porcentaje de anticuerpos posvacunaci&#243;n fue similar entre hombres y mujeres &#40;mediana 97&#44;24&#37;&#41;&#46; La frecuencia de los ESAVI adinamia &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0243&#41;&#44; escalofr&#237;os &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0085&#41;&#44; artralgia &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0227&#41; y dolor en zona de aplicaci&#243;n &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0096&#41; fueron m&#225;s frecuentes en las mujeres&#46; El genotipo GA de rs1800629 se asoci&#243; con fiebre &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0131&#41; y artralgia &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0058&#41; post-vacunaci&#243;n&#44; pero no con la producci&#243;n de anticuerpos neutralizantes&#46; La variante rs2228145 no se asoci&#243; con la producci&#243;n de anticuerpos ni con la frecuencia de ESAVI&#46;</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Conclusi&#243;n</span><p id="sp0085" class="elsevierStyleSimplePara elsevierViewall">las variantes rs1800629 en <span class="elsevierStyleItalic">TNF</span> y rs222815 en <span class="elsevierStyleItalic">IL6R</span> no se asocian con la producci&#243;n de anticuerpos neutralizantes contra SARS-CoV-2 despu&#233;s de recibir el esquema AZD1222 en la poblaci&#243;n del occidente de M&#233;xico&#59; sin embargo&#44; los resultados sugieren que la variante rs1800629 incrementa la frecuencia de los ESAVI fiebre y artralgia&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "as0005"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "as0010"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "as0015"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "as0020"
            "titulo" => "Conclusi&#243;n"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="as0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Introduction</span><p id="sp0090" class="elsevierStyleSimplePara elsevierViewall">In this research&#44; we evaluated the association of genetic variants rs1800629 in <span class="elsevierStyleItalic">TNF</span> and rs2228145 in <span class="elsevierStyleItalic">IL6R</span> with production of neutralizing antibodies against SARS-CoV-2 and the frequency of adverse effects following immunization &#40;AEFIs&#41; in adult population from Western of Mexico that received AZD1222 vaccination&#46;</p></span> <span id="as0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Methods</span><p id="sp0095" class="elsevierStyleSimplePara elsevierViewall">One hundred-seventeen adults were evaluated &#40;33 years &#91;23-40&#93;&#44; 65&#37; women&#41;&#46; The self-reported frequency of AEFIs was recorded and the percentage of post-vaccination neutralizing antibodies was quantified&#46; The identification of rs1800629 variant in <span class="elsevierStyleItalic">TNF</span> and rs2228145 in <span class="elsevierStyleItalic">IL6R</span> was performed by qPCR&#46;</p></span> <span id="as0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Results</span><p id="sp0100" class="elsevierStyleSimplePara elsevierViewall">The genotype frequencies of rs1800629 variant were&#58; GG &#40;86&#37;&#41; and GA &#40;14&#37;&#41;&#44; and for rs2228145 variant were&#58; AA &#40;20&#37;&#41;&#44; CA &#40;48&#37;&#41; and CC &#40;32&#37;&#41;&#46; The percentage of post-vaccination antibodies was similar between men and women &#40;median&#44; 97&#46;24&#37;&#41;&#46; An association was found between the frequency of AEFIs with the sex&#59; being adynamia &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0243&#41;&#44; chills &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0085&#41;&#44; arthralgia &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0227&#41; and pain in application area &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0096&#41; more frequent in women&#46; The GA genotype of rs1800629 variant showed an association with fever &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0131&#41; and arthralgia &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0058&#41; post-vaccination&#44; but no relationship was found with the production of neutralizing antibodies after AZD1222 vaccination&#46; The rs2228145 variant was not associated with the production of antibodies nor with the AEFIs reported&#46;</p></span> <span id="as0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Conclusion</span><p id="sp0105" class="elsevierStyleSimplePara elsevierViewall">The genetic variants rs1800629 in <span class="elsevierStyleItalic">TNF</span> and rs222815 in <span class="elsevierStyleItalic">IL6R</span> are not associated with the production of neutralizing antibodies against SARS-CoV-2 after receiving AZD1222 scheme in population from western of Mexico&#59; however&#44; the results suggest that rs1800629 variant increases the frequency of post-vaccination events&#44; particularly fever and arthralgia&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "as0025"
            "titulo" => "Introduction"
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            "identificador" => "as0030"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "as0035"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "as0040"
            "titulo" => "Conclusion"
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        ]
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          "es" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">a&#41; Porcentajes de neutralizaci&#243;n contra la prote&#237;na espiga del SARS-CoV-2 con respecto al sexo&#59; prueba U de Mann-Whitney&#46; b&#41; Porcentajes de neutralizaci&#243;n contra la prote&#237;na S del SARS-CoV-2 con respecto a los genotipos de la variante rs1800629&#59; prueba U de Mann-Whitney&#46; c&#41; Porcentajes de neutralizaci&#243;n contra la prote&#237;na S del SARS-CoV-2 con respecto a los genotipos de la variante rs2228145&#59; prueba Kruskal-Wallis&#46; Las l&#237;neas horizontales representan mediana y rango intercuartil &#40;P25&#37;-P75&#37;&#41;&#46;</p>"
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          "leyenda" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">IMC&#58; &#237;ndice de masa corporal&#46;</p><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Los datos se presentan como media &#177; desviaci&#243;n est&#225;ndar o mediana &#40;P25&#37;-P75&#37;&#41;&#44; seg&#250;n su distribuci&#243;n&#46; Los valores significativos se muestran en negrita&#46;</p><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Prueba utilizada seg&#250;n la normalidad de los datos&#46;</p>"
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Grasa corporal &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;25-40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#177; 14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#177; 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;0001</span><a class="elsevierStyleCrossRef" href="#tf0010"><span class="elsevierStyleSup"><span class="elsevierStyleBold">b</span></span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IMC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;23-31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#177; 7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#177; 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;0661<a class="elsevierStyleCrossRef" href="#tf0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&#237;as posvacunaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;22-58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;23-63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;20-51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;5371<a class="elsevierStyleCrossRef" href="#tf0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="5" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Enfermedades cr&#243;nicas</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diabetes mellitus tipo 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;8 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;7 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hipertensi&#243;n arterial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;7 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;5 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Colitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Arritmia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hep&#225;tica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Asma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;4 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;6 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tiroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dislipidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resistencia a la insulina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&#225;ncer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Taquicardia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;8 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Obesidad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#44;9 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;1 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#44;2 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="5" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antecedentes cl&#237;nicos</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alergias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;5 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;6 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;9&#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">COVID-19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;5 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44;4 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;3 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total&#40;<span class="elsevierStyleItalic">n &#61;</span> 117&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Masculino&#40;<span class="elsevierStyleItalic">n &#61;</span> 45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Femenino&#40;<span class="elsevierStyleItalic">n &#61;</span> 72&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR &#40;IC 95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Genotipos</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">rs1800629</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#44;3 &#40;101&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&#44;4 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&#44;5 &#40;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;783</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;7 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;6 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;5 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;775 &#40;0&#44;272-2&#44;062&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">--&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">rs2228145</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#44;3 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;6 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;839</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48 &#40;55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#44;9 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#44;2 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;9490 &#40;0&#44;411-2&#44;262&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&#44;4 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2947<a class="elsevierStyleCrossRef" href="#tf0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adinamia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#44;7 &#40;57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#44;6 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#44;9 &#40;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;0243</span><a class="elsevierStyleCrossRef" href="#tf0020"><span class="elsevierStyleSup"><span class="elsevierStyleBold">b</span></span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Irritabilidad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44;7 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#44;8 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#44;2 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;1651<a class="elsevierStyleCrossRef" href="#tf0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Limitaci&#243;n del movimiento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;8 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;1 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;7934<a class="elsevierStyleCrossRef" href="#tf0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Escalofr&#237;os&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#44;7 &#40;57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#44;3 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#44;3 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;0085</span><a class="elsevierStyleCrossRef" href="#tf0020"><span class="elsevierStyleSup"><span class="elsevierStyleBold">b</span></span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mareo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;5323<a class="elsevierStyleCrossRef" href="#tf0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hiporexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;3 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;9 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#44;4 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;1874<a class="elsevierStyleCrossRef" href="#tf0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Edema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;4 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;2 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS<a class="elsevierStyleCrossRef" href="#tf0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#225;usea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;5 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;9 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;1 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;1917<a class="elsevierStyleCrossRef" href="#tf0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">V&#243;mito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;2 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;6 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;6476<a class="elsevierStyleCrossRef" href="#tf0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diarrea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;5 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;2 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;5 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;0862<a class="elsevierStyleCrossRef" href="#tf0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Taquicardia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;8 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;7 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;9 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS<a class="elsevierStyleCrossRef" href="#tf0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rinorrea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;2 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;7 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;5 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3664<a class="elsevierStyleCrossRef" href="#tf0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;4 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;7 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;1 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;5270<a class="elsevierStyleCrossRef" href="#tf0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mialgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">35&#44;6 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">52&#44;8 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#44;0691<a class="elsevierStyleCrossRef" href="#tf0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Generales &#37; &#40;n&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#44;2 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;1116<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cefalea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#44;4 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;5 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;8146<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;4047<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Astenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#44;3 &#40;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;5 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;7637<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#44;2 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 &#40;26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;3911<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adinamia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#44;5 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;5 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2352<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#44;7 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;5714<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Irritabilidad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;8 &#40;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;3 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;5397<a class="elsevierStyleCrossRef" href="#tf0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">20&#44;8 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">27 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;8498<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Limitaci&#243;n de movimiento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#44;8 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">31&#44;3 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;1792<a class="elsevierStyleCrossRef" href="#tf0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">8&#44;3 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">18 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">27 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;1831<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Escalofr&#237;os&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#44;5 &#40;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#44;3 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;5165<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">37&#44;5 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">57 &#40;32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;1975<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mareo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#44;8 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;3 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;5224<a class="elsevierStyleCrossRef" href="#tf0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;9537<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hiporexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;8 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;5 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS<a class="elsevierStyleCrossRef" href="#tf0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;0908<a class="elsevierStyleCrossRef" href="#tf0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#225;useas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Rinorrea&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Dolor far&#237;ngeo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Tos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">Disnea&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Mialgia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">Artralgia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">30 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Reacci&#243;n local</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">Induraci&#243;n&#47;n&#243;dulo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&#44;8 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NS<a class="elsevierStyleCrossRef" href="#tf0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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Información del artículo
ISSN: 15769887
Idioma original: Español
DOI:10.1016/j.vacun.2023.12.004
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